Epidemiology of sleep apnoea/hypopnoea syndrome and sleep-disordered breathing

Eur Respir J 2009; 33: 907 914 DOI: 10.1183/09031936.00180108 CopyrightßERS Journals Ltd 2009 SERIES THE GENETIC AND CARDIOVASCULAR ASPECTS OF OBSTRUCTIVE SLEEP APNOEA/HYPOPNOEA SYNDROME Edited by R.L. Riha and W.T. McNicholas Number 3 in this Series Epidemiology of sleep apnoea/hypopnoea syndrome and sleep-disordered breathing P. Jennum* and R.L. Riha # ABSTRACT: Epidemiological studies have revealed a high prevalence of sleep-disordered breathing in the community (up to 20%). A subset of these patients has concurrent symptoms of excessive daytime sleepiness attributable to their nocturnal breathing disorder and is classified as having obstructive sleep apnoea/hypopnoea syndrome (4 5% of the middle-aged population). There is strong evidence for an association of sleep apnoea with cardiovascular and cerebrovascular morbidity, as well as adverse public health consequences. Treatment and diagnosis have remained largely unchanged over the past 25 yrs. In moderate-to-severe obstructive sleep apnoea/hypopnoea syndrome, treatment with continuous positive airway pressure has been shown to be effective. Questions remain as to how to screen patients with sleep-disordered breathing. Should time-consuming diagnostic procedures with high sensitivity and specificity be employed, or should simpler methods be applied for screening populations at risk, e.g. in the primary care sector? KEYWORDS: Epidemiology, sleep apnoea, sleep-disordered breathing The epidemiology of obstructive sleep apnoea (OSA)/hypopnoea syndrome (OSAHS) has been described in a significant number of studies. OSAHS affects,2 4% of the middle-aged population and is defined on the basis of symptoms of daytime sleepiness and objective measures of disordered breathing during sleep. Obstruction of the upper airway during sleep, resulting in repetitive breathing pauses accompanied by oxygen desaturation and arousal from sleep, is characteristic of OSAHS. This results in diurnal sleepiness leading to cognitive impairment. Sleepdisordered breathing (SDB; snoring and associated apnoeas) is common and affects up to 20% of the population. OSAHS is common in adults and children. OSAHS is an independent risk factor for hypertension and is associated with cardiovascular and cerebrovascular morbidity. OSAHS has consequences for public health (driving, accidents at work) and the economy. The benefits and effects of continuous positive airway pressure (CPAP) treatment have been described in prospective studies. Despite increasing awareness of the condition and improved diagnostic procedures, most patients in the community remain undiagnosed and untreated. This is especially true of patients who may be at high risk for additional complications, e.g. those with metabolic syndrome, diabetes, or cardiac, cerebrovascular or other neurological diseases. Few or no public health programmes have included systematic screening for OSAHS. Traditionally, OSAHS is diagnosed using in-hospital, supervised overnight polysomnography (PSG) followed by manual titration of CPAP. This is costly, both time-wise and economically, and since the capacity of this procedure is limited, waiting lists tend to lengthen. This calls for discussion of an organisational model not only for the identification and management, but also for the prevention, of OSAHS and its consequences. The present article focuses on the epidemiological aspects of OSAHS and SDB, risk associations, socioeconomic consequences and organisational aspects of diagnosing and managing sleep apnoea. Previous article in this series: No. 1: MacLeod AK, Liewald DCM, McGilchrist MM, Morris AD, Kerr SM, Porteous DJ. Some principles and practices of genetic biobanking studies. Eur Respir J 2009; 33: 419 425. No. 2: Riha RL, Gislasson T, Diefenbach K. The phenotype and genotype of adult obstructive sleep apnoea/hypopnoea syndrome. Eur Respir J 2009; 33: 646 655. AFFILIATIONS *Danish Centre for Sleep Medicine Glostrup, Denmark. # Dept of Sleep Medicine Royal Infirmary of Edinburgh, Edinburgh, UK. CORRESPONDENCE P. Jennum Danish Centre for Sleep Medicine, Dept of Clinical Neurophysiology, Faculty of Health Sciences University of Copenhagen Glostrup Hospital DK 2600 Glostrup Denmark Fax: 45 43233933 E-mail: poje@glo.regionh.dk Received: November 27 2008 Accepted after revision: January 13 2009 STATEMENT OF INTEREST None declared. European Respiratory Journal Print ISSN 0903-1936 Online ISSN 1399-3003 c EUROPEAN RESPIRATORY JOURNAL VOLUME 33 NUMBER 4 907

EPIDEMIOLOGY OF SLEEP APNOEA P. JENNUM AND R.L. RIHA EPIDEMIOLOGY Sleep apnoea has been recognised throughout human history, dating as far back as the 4th century BC. Numerous reports throughout the 19th century and the early part of the 20th century AD gave way to systematically conducted studies on patients with OSAHS and related syndromes [1]. OSAHS was first properly documented in neurophysiological sleep laboratories using techniques developed for the investigation of other conditions such as depression and narcolepsy. OSAHS was first described as such in 1965 [2] and there has since been an explosion in the facilities for its diagnosis and treatment as well as a rapid advancement in the understanding of its far-reaching consequences. Reporting of OSAHS was initially confined to case series, but more recently, large-scale epidemiological studies have attempted to answer questions on the incidence and prevalence of OSAHS. However, few of these have used ideal methods and it is therefore difficult to draw firm conclusions from them. Generally, the best-conducted studies, in terms of method and rigour of technique employed, have found a prevalence of OSAHS in the middle-aged male population of up to 4% [3]. The study showing the lowest quoted prevalence may have underestimated the occurrence of OSAHS in the population by using oximetry alone, with more than five 4% dips in pulse oximetry-measured arterial oxygen saturation per hour, as an initial screening measure [4], while those studies showing the highest prevalences may have overestimated the prevalence by including central apnoeas and breath-holds occurring during wakefulness [5] using inductance plethysmography at home. Assessment of sleepiness differed between the studies on account of using self-devised questionnaires specific to each study. Fewer studies exist examining the prevalence of OSAHS in females but it is probably half that of males, at 0.5 1% [5]. OSAHS occurs throughout the entire lifespan, from neonates to the elderly. In adults, the frequency of disordered breathing during sleep increases with age and is poorly associated with an increased incidence of daytime sleepiness or other symptoms of OSAHS [6 10]. ASSESSMENT OF OSAHS As discussed above, a definitive diagnosis of OSAHS requires objective recording and measurement of sleep and breathing during the night in addition to a measure of daytime sleepiness (objective or subjective) and other symptoms. SDB An objective measure of SDB at night is generally required to confirm the diagnosis of OSAHS. The method most widely used, and which is considered by some to be the gold standard for diagnosis despite limited evidence, is overnight PSG. An American Academy of Sleep Medicine (AASM) Task Force published indications for PSG in 1997 [11] and measurement techniques and syndrome definitions in 1999 [12]. Most PSG studies monitor the following routinely: nasal and/or oral airflow; thoracoabdominal movement; snoring; electroencephalogram (EEG); electro-oculogram; electromyogram; and oxygen saturation. Signal collection and interpretation is usually computerised, but manual scoring of the trace should still be performed using guidelines for interpretation of the EEG published in 1968 by RECHTSCHAFFEN and KALES [13], and the 1999 AASM criteria [12]. Full-night PSG is generally performed, but split-night studies are also used [14], in which the first half of the study night is used for diagnosis and the second half to monitor treatment response using CPAP. Cardiorespiratory monitoring alone can also be used. This involves the measurement of airflow, respiratory effort, oxygen saturation and cardiac frequency, but not EEG. The great advantages of these systems are price, portability and the ability of patients to monitor themselves at home. FERBER et al. [15] reviewed seven studies of portable ambulatory monitoring systems and reported a sensitivity of 78 100% and a specificity of 67 100% in comparison with in-lab PSG, although ambulatory monitoring is of course not a gold standard. Overnight oximetry is sometimes used as a screening test for identifying patients who are at risk of significant OSAHS, but this should never be seen as a substitute for in-lab PSG or home cardiorespiratory monitoring. There are severe limitations inherent in this technique used in isolation, including the inability to detect apnoeas or hypopnoeas not associated with oxygen desaturation and the upper airway resistance syndrome. Furthermore, nocturnal oxygen desaturation may be related to sleep hypoventilation without associated upper airways obstruction, e.g. in chronic obstructive pulmonary disease (COPD), severe kyphoscoliosis, muscular dystrophy and morbid obesity, and in the setting of periodic breathing associated with severe heart failure. Daytime sleepiness Sleepiness is difficult to define (see [16] for a review). Sleepiness can be regarded as normal sleepiness (a result of the normal circadian rhythm) and pathological sleepiness (a result of altered sleep scheduling). Pathological sleepiness can be further subdivided into habitual (e.g. as the result of recurring precipitants of sleepiness such as OSA) or occasional (e.g. as the result of jet lag or medication). As proposed by CLUYDTS et al. [16], sleepiness can be recognised using a number of different measures. 1) Inferring sleepiness from behaviour, e.g. observation of yawning frequency, actigraphy, facial expression or performance tests such as the driving simulator, psychomotor vigilance tests and reaction time tests. 2) Self-evaluation of sleepiness using rating scales, e.g. the Stanford Sleepiness Scale to measure sleepiness at a given instant, and the Epworth Sleepiness Score (ESS) to measure sleepiness averaged over a month. 3) Direct electrophysiological measures, e.g. multiple sleep latency test and multiple wakefulness test [17], pupillometry and cerebral evoked potentials. In respect to the diagnosis and monitoring of OSAHS, probably the most widely used and best-validated scale assessing daytime sleepiness is the ESS, first devised in 1991 [18]. Its advantages include ease of administration and low cost. It assesses global level of sleepiness and is independent of short-term variations in sleepiness with the time of day and also of inter-day variations [19]. The ESS aims to measure the general level of daytime sleepiness as a stable individual 908 VOLUME 33 NUMBER 4 EUROPEAN RESPIRATORY JOURNAL

P. JENNUM AND R.L. RIHA EPIDEMIOLOGY OF SLEEP APNOEA characteristic and has satisfactory test retest reliability [20]. The ESS is also able to discriminate between normal and pathological sleepiness [20]. The accuracy of the ESS depends on the awareness of subjects falling asleep, which may not always be the case [21]. Rating of the subject s sleepiness by another person may be more precise [22]. The ESS does not correlate strongly with more objective measures of daytime sleepiness such as the multiple sleep latency test (MSLT) or maintenance of wakefulness test (MWT) [23], but this is in keeping with the fact that sleepiness is not a unitary concept. ESS reproducibly reflects changes in sleepiness with therapy in OSAHS [24]. Because of its reliability and its ability to differentiate between abnormal and normal levels of sleepiness, as well as for its ease of administration, the ESS is one of the most widely used measures of sleepiness. In summary, self-reporting of snoring, nocturnal gasping or apnoeas and measures of sleepiness (e.g. ESS) correspond relatively poorly with objective measures, such as sound recording, apnoea/hypopnoea index (AHI) and MSLTs/ MWTs [25]. Any relationship between these factors depends on the standardisation and the value of the reference test/gold standard and is subject to high variability in the validity of questionnaire and test evaluation. Complaints of sleepiness and/or other indications of hypersomnia are related to many other conditions, not just SDB, which weakens the relationship further. Epidemiological studies have used a variety of methods to measure OSA, including self-reported markers such as snoring, apnoeas, daytime sleepiness, in-laboratory PSG, unattended in-home PSG, and unattended polygraphic or other recordings of a few physiological parameters. Studies using objective measures of apnoea and hypopnoea have employed variable respiratory event definitions. Moreover, there has been no standardisation of the method used to quantify airflow, with methods such as thermistry, inductance plethysmography and nasal cannula/pressure transducer systems providing different sensitivities to changes in airflow. Like other conditions based on a severity continuum, the definition of the units of the continuum and the ultimate thresholds used to designate the presence of OSA will affect the magnitude of prevalence and estimates of associations with risk factors and outcomes. The use of more-restrictive definitions of apnoea and hypopnoea, higher AHI cut-off points, or an additional requirement for symptoms of sleepiness, will obviously lower prevalence estimates and affect values expressing associations, such as odds ratios. Like other conditions, OSAHS presents a severity spectrum which affects the estimates of prevalences. Studies have consistently found that symptomatic OSAHS occurs in o2 4% of the adult population. Studies evaluating the occurrence of SDB, independently of symptoms, show a much higher prevalence of 6 24% among adults (tables 1 3). SEX AND AGE OSAHS is more common in males than in females, with a ratio of 2:1. Menopause is a risk factor for sleep apnoea [26]. OSAHS prevalence increases in mid-life, but the existence of OSAHS in childhood, adolescence and older age means that there is no simple positive correlation of OSAHS with age [27]. A multimodal distribution of prevalence by age is often indicative of distinct disease subtypes with different aetiologies and health consequences. SDB occurs commonly in populations aged.65 yrs (tables 1 3), but there is controversy regarding its significance in older people and its relationship to OSAHS that occurs in middle age [28, 29]. RISK ASSOCIATIONS Smoking Smoking is one of the strongest risk factors for cardiovascular disease. The association with OSAHS is relatively weak, but smoking may interact with and add to the cardiovascular risk associated with OSA [30]. Genetics/family history Reports published in the 1990s suggested a relationship between self-reported snoring and familial occurrence of snoring and sleep apnoea, with a relative risk association of 3 5 [31 33]. The risk has been demonstrated to increase if both parents are affected. A number of studies have documented this association. A recent review of this evidence has evaluated this relationship [34]. In addressing this topic, future studies should address the hereditary components of OSAHS by subdividing the disease according to different subgroups, e.g. sleep apnoea with age of onset of disease, hypertension, metabolic syndrome, propensity to cerebrovascular disease and other risk associations. TABLE 1 Age yrs Age- and sex-specific prevalence rates of the apnoea/hypopnoea index (AHI) based on polysomnographic (PSG) results for a sample of 1,050 males and 1,098 females from the Vitoria- Gasteiz region of Spain AHI o5 o10 o15 o20 o30 Males 30 39 9.0 (2 16) 7.6 (0 15) 2.7 (1 5) 2.1 (0 4) 2.1 (0 4) 40 49 25.6 (14 37) 18.2 (9 27) 15.5 (7 24) 10.1 (5 15) 7.0 (3 11) 50 59 27.9 (17 38) 24.1 (15 34) 19.4 (11 27) 14.7 (8 21) 11.4(6 17) 60 70 52.1 (33 71) 32.2 (17 48) 24.2 (12 37) 15.0 (8 22) 8.6 (4 14) Females 30 39 3.4 (0 7) 1.7 (0 4) 0.9 (0 2) 40 49 14.5 (3 25) 9.7 (0 19) 50 59 35.0 (20 50) 16.2 (5 27) 8.6 (1 17) 8.3 (0 16) 4.3 (0 10) 60 70 46.9 (31 63) 25.6 (13 38) 15.9 (6 26) 13.0 (3 22) 5.9 (0 13) Data are presented as % (95% confidence interval). Data were collected as follows. The MESAM IV portable recording system (Medizintechnik für Artzund Patient, Munich, Germany) was used overnight. PSG was recorded using Alice 3 (Respironics, Pittsburgh, PA, USA). Manual scoring using conventional criteria was employed. An abnormal breathing event was defined as complete cessation of airflow for o10 s (apnoea) or a discernible 50% reduction in respiratory airflow accompanied by a decrease of o4% in arterial oxygen saturation measured by pulse oximetry and/or electroencephalogram arousal (hypopnoea). Arousals were defined according to American Sleep Disorders Association criteria [15]. Reproduced from [6], with permission from the publisher. c EUROPEAN RESPIRATORY JOURNAL VOLUME 33 NUMBER 4 909

EPIDEMIOLOGY OF SLEEP APNOEA P. JENNUM AND R.L. RIHA TABLE 2 Age- and sex-specific prevalence rates of the apnoea/hypopnoea index (AHI) based on polysomnographic (PSG) results for a sample of 352 males and 250 females from Wisconsin, USA TABLE 3 Prevalence rates of the apnoea and hypopnoea index (AHI) by age based on polysomnographic (PSG) results for a sample of 741 males from two counties in Southern Pennsylvania, USA Age yrs AHI Age yrs Subjects AHI o5 o10 o15 o5 o10 o20 Males 30 39 17.0 (9.6 25) 12.0 (5.4 19) 6.2 (1.9 10) 40 49 25.0 (18 32) 18.0 (11 24) 11.0 (6.7 16) 50 60 31.0 (21 40) 14.0 (7.5 20) 9.1 (5.1 13) Females 30 39 6.5 (1.4 11) 4.9 (0.6 9.8) 4.4 (1.1 7.3) 40 49 8.7 (4.2 13) 4.9 (1.7 8.1) 3.7 (1.0 6.5) 50 60 16.0 (5.2 26) 5.9 (0.0 12.0) 4.0 (0.0 10) Data are presented as % (95% confidence interval). Data were collected as follows. Overnight in-lab PSG recording was carried out in sound-attenuated, light- and temperature-controlled rooms using standard set-up and a 16- channel polygraph (Model 78d; Grass Instrument, Quincy, MA, USA). Manual scoring using conventional criteria was employed. An abnormal breathing event was defined as complete cessation of airflow for o10 s (apnoea) or a discernible 50% reduction in respiratory airflow accompanied by a decrease of o4% in arterial oxygen saturation measured by pulse oximetry. Reproduced from [3], with permission from the publisher. Obesity and metabolic syndrome There is strong epidemiological and clinical evidence for a relationship between sleep apnoea, central obesity and metabolic syndrome. Despite the lack of controlled studies, several studies have presented data showing that weight reduction through dieting or bariatric surgery is followed by a reduction in AHI and incidence of diabetes, improved glucose control and reductions in hyper-triglyceridaemia [35 37]. This important area will be discussed further in the last paper in the current series. Polycystic ovary syndrome There is some evidence that sleep apnoea is associated with polycystic ovary syndrome [38, 39]; however, no epidemiological, cross-sectional or prospective studies have addressed this important issue. CONSEQUENCES OF OSA Morbidity and mortality associated with OSAHS Untreated OSAHS can contribute to the development or progression of other disorders. OSAHS has now been shown to be a cause for systemic hypertension [40] and there is some evidence suggesting that it can also cause pulmonary hypertension [41, 42]. OSAHS is also associated with ischaemic heart disease. SDB has been found to be a significant clinical feature in a proportion of patients with cerebrovascular disease: stroke and transient ischaemic attacks [40]. However, published results are contradictory, with some showing no increase in OSAHS in those with transient ischaemic attacks [43], while others show a high prevalence of OSAHS in those with stroke (see [44] for review). 20 44 236 7.9 (5.0 12.1) 3.2 (1.6 6.4) 1.7 (0.6 4.4) 45 64 430 19.7 (16.2 23.7) 11.8 (9.1 15.3) 23.9 (15.7 34.9) 65 100 75 30.5 (21.1 41.7) 23.9 (15.7 34.9) 13.3 (7.3 23) Data are presented as n or % (95% confidence interval). Data were collected as follows. Overnight in-lab PSG recording was carried out in sound-attenuated, light- and temperature-controlled rooms using standard set-up and a 16- channel polygraph (Model 78d; Grass Instrument, Quincy, MA, USA). Manual scoring using conventional criteria was employed. An abnormal breathing event was defined as complete cessation of airflow for o10 s (apnoea) or a discernible 50% reduction in respiratory airflow accompanied by a decrease of o4% in arterial oxygen saturation measured by pulse oximetry. Reproduced from [7], with permission from the publisher. Treating OSAHS in stroke is also controversial. Some studies show a significant reduction in SDB and improvement in quality of life, while others do not [45, 46]. Patients with OSAHS and moderate-to-severe coexistent lung disease, such as COPD, are more likely to develop type II respiratory failure that will improve with treatment of the obstructive apnoeas [47, 48]. Likewise, nocturnal asthma may be worsened by sleep apnoea and treatment may lead to improvement [49]. OSAHS leads to neuropsychological impairment that includes deficits in attention, concentration, vigilance, manual dexterity, visuomotor skills, memory, verbal fluency and executive function [50]. Perhaps the most important complication of OSAHS, and the one that has the greatest impact from the public health perspective, is driving accidents. More than onethird of patients with OSAHS report having had an accident or near-accident on account of falling asleep while driving [51]. There is also objective evidence of 1.3 12-fold increases in accident rates among those with sleep apnoea, and accident rates in OSAHS patients have been found to be 1.3 to seven times higher than those in the general population [52 54]. Vigilance testing and driving simulators in studies assessing driving performance in patients with OSAHS reveal that performance is markedly reduced and the impairment is not limited to periods when patients actually fall asleep but also occurs when they are awake, owing to reduced vigilance. There is also evidence that OSAHS patients have a 50% increased risk of workplace accidents [55, 56]. OSAHS thus leads to several complications, including: impairment in education, quality of life and work capacity; traffic accidents; cardiac and cerebrovascular morbidity and mortality; and increased economic burden. Hypertension A relationship between sleep apnoea, snoring and hypertension was proposed in the first half of the 1980s. This relationship was 910 VOLUME 33 NUMBER 4 EUROPEAN RESPIRATORY JOURNAL

P. JENNUM AND R.L. RIHA EPIDEMIOLOGY OF SLEEP APNOEA initially supported by epidemiological studies using selfreported snoring as a surrogate marker for sleep apnoea [55, 57]. Later follow-up studies suggested that sleep apnoea was correlated with increased cardiovascular risk [58]. Although snoring is associated with hypertension, several studies questioned the link, taking other risk factors into consideration [59]. This is due to the problem with self-reported snoring: it shows only a partial relationship to sleep apnoea, with moderate sensitivity and specificity. Since then, several studies have shown a relationship between sleep apnoea, apnoea severity and the occurrence of hypertension, independently of risk factors, such as age and obesity [40]. Cardiac disease Over the past 25 yrs, several studies have documented snoring and OSAHS as risk factors for cardiac disease (artherosclerotic, acute myocardial infarction, arrhythmias). Morbidity and mortality risk is increased in the context of SDB, even when taking other risk factors into consideration [40]. Sleep apnoea and stroke Based on cross-sectional epidemiological studies primarily using self-reported snoring, a relationship between snoring and stroke was proposed in the mid-1980s. Prospective studies have supported this relationship. The drawback of these studies, however, was the inaccuracy of the report of snoring due to the sensitivity, specificity and the individuality of this symptom, which weakens a potential relationship between sleep apnoea and stroke. Case control studies suggest a potential relationship based upon historical report of sleep apnoea and PSG findings in stroke patients compared with control groups [60, 61]. There are, however, several issues in these patients, especially patients with stroke and sleep-related breathing problems. These include selection problems and stroke-induced SDB (e.g. pseudo-bulbar OSA, central apnoea and hypoventilation) which may add to the occurrences of sleep-related breathing disorders [62]. Traffic accidents Noncommercial drivers with sleep apnoea are at a statistically significant increased risk of having a motor vehicle crash. Magnitude of daytime sleepiness and the severity of SDB were correlated with crash risk, while full treatment of sleep apnoea improves driver performance [63]. Untreated OSAHS increases societal costs due to traffic accidents and their consequences [64 66]. Socioeconomic consequences The social and cardiovascular consequences of OSAHS seem most pronounced among patients of low socioeconomic status. This was found to be the case in a clinic population [67], but in a discharge register study from Sweden, socioeconomic status had a minor effect on the likelihood of hospitalisation and it was suggested that other factors, e.g. smoking and obesity, may influence this observed relationship [68]. It should be noted, however, that there is a tendency towards lower screening and diagnostic activity among people of lower social status. OSAHS presents a significant socioeconomic burden due to comorbidity, healthcare utilisation in the primary and secondary healthcare sectors, use of medication, effects on employment and lost income. Treatment of OSAHS causes reduced morbidity, mortality and hospitalisation rates and this has been demonstrated to be cost effective [69 73]. SCREENING AND MANAGEMENT OF SLEEP APNOEA Undiagnosed OSAHS is likely to be highly prevalent, even in countries where diagnostic facilities have been available for a long time. A significant proportion of the potential for improved diagnosis is in the primary care sector, and in high-risk groups, e.g. patients with acute and chronic cardiovascular or cerebrovascular disease, or diabetics. There is a need to evaluate the optimal organisational model for patient identification and management. Few studies have presented the optimal economic model for the evaluation of OSAHS. In a Danish Health Technology Assessment, the use of ambulatory portable diagnostic procedures using partial polygraphy followed by auto-adjusted CPAP was superior to the use of in-hospital, supervised PSG (which is time consuming and costly) and oximetry (which has low sensitivity and diagnostic accuracy) among patients without major comorbidity in the primary care sector [74]. Similar results have been obtained by others, who found oximetry to present low diagnostic accuracy, but also pointed out the use of split-night PSG studies as an alternative diagnostic and therapeutic approach [75]. Thus, there is a need to evaluate the organisation of diagnosing and managing patients with OSAHS, with and without major comorbidities. In patients without major comorbidity suspected of OSAHS, a portable study approach is possible [76], whereas in patients with significant neurological, cardiac or pulmonary disease it is likely that a supervised study is desirable [77]. CONCLUSION In conclusion, it is impossible, in view of the vast quantity of literature that has burgeoned in the field of obstructive sleep apnoea/hypopnoea syndrome, to present an exhaustive overview of all its aspects. However, the following main messages remain: obstructive sleep apnoea/hypopnoea syndrome and sleep-disordered breathing are very common, affecting a significant proportion of the population and, when untreated, cause significant increased social, cardiac and cerebrovascular morbidity and mortality; a significant proportion of patients with obstructive sleep apnoea/hypopnoea syndrome remain undiagnosed and untreated due to inadequate resources for case detection and investigation. There is a need to identify optimal organisational and economic models to identify patients at risk for additional screening and management, especially in at-risk populations. ACKNOWLEDGEMENTS Thanks to S. Rafferty (Royal Infirmary of Edinburgh, Edinburgh, UK) for her help in the preparation of the present manuscript. REFERENCES 1 Lavie P. Nothing new under the moon. Historical accounts of sleep apnea syndrome. Arch Intern Med 1984; 144: 2025 2028. 2 Jung R, Kuhlo W. Neurophysiological studies of abnormal night sleep and the Pickwickian syndrome. Prog Brain Res 1965; 18: 140 159. c EUROPEAN RESPIRATORY JOURNAL VOLUME 33 NUMBER 4 911

EPIDEMIOLOGY OF SLEEP APNOEA P. JENNUM AND R.L. RIHA 3 Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993; 328: 1230 1235. 4 Stradling JR, Crosby JH. Predictors and prevalence of obstructive sleep apnoea and snoring in 1001 middle aged men. Thorax 1991; 46: 85 90. 5 Jennum P, Sjøl A. Epidemiology of snoring and obstructive sleep apnoea in a Danish population, age 30 60. J Sleep Res 1992; 1: 240 244. 6 Durán J, Esnaola S, Rubio R, Iztueta A. Obstructive sleep apnea hypopnea and related clinical features in a population-based sample of subjects aged 30 to 70 yr. Am J Respir Crit Care Med 2001; 163: 685 689. 7 Bixler EO, Vgontzas AN, Ten Have T, Tyson K, Kales A. Effects of age on sleep apnea in men: I. Prevalence and severity. Am J Respir Crit Care Med 1998; 157: 144 148. 8 Bixler EO, Vgontzas AN, Lin HM, et al. Prevalence of sleepdisordered breathing in women: effects of gender. Am J Respir Crit Care Med 2001; 1623: 608 613. 9 Gislason T, Almqvist M, Eriksson G, Taube A, Boman G. Prevalence of sleep apnea syndrome among Swedish men an epidemiological study. J Clin Epidemiol 1988; 41: 571 576. 10 Puvanendran K, Goh KL. From snoring to sleep apnea in a Singapore population. Sleep Res Online 1999; 2: 11 14. 11 Polysomnography Task Force, American Sleep Disorders Association Standards of Practice Committee, Practice parameters for the indications for polysomnography and related procedures. Sleep 1997; 20: 406 422. 12 American Academy of Sleep Medicine Task Force, Sleeprelated breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 1999; 22: 667 689. 13 Rechtschaffen A, Kales S, eds. A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. Bethesda, National Institutes of Health, 1968. 14 Pepperell JC, Davies RJ, Stradling JR. Sleep studies for sleep apnoea. Physiol Meas 2002; 23: R39 R74. 15 Ferber R, Millman R, Coppola M, et al. Portable recording in the assessment of obstructive sleep apnea. ASDA standards of practice. Sleep 1994; 17: 378 392. 16 Cluydts R, De Valck E, Verstraeten E, Theys P. Daytime sleepiness and its evaluation. Sleep Med Rev 2002; 6: 83 96. 17 Littner MR, Kushida C, Wise M, et al. Practice parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test. Sleep 2005; 28: 113 121. 18 Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991; 14: 540 545. 19 Johns MW. Sleepiness in different situations measured by the Epworth Sleepiness Scale. Sleep 1994; 17: 703 710. 20 Johns MW. Reliability and factor analysis of the Epworth Sleepiness Scale. Sleep 1992; 15: 376 381. 21 Reyner LA, Horne JA. Falling asleep whilst driving: are drivers aware of prior sleepiness? Int J Legal Med 1998; 111: 120 123. 22 Kingshott RN, Sime PJ, Engleman HM, Douglas NJ. Self assessment of daytime sleepiness: patient versus partner. Thorax 1995; 50: 994 995. 23 Benbadis SR, Mascha E, Perry MC, Wolgamuth BR, Smolley LA, Dinner DS. Association between the Epworth sleepiness scale and the multiple sleep latency test in a clinical population. Ann Intern Med 1999; 130: 289 292. 24 Patel SR, White DP, Malhotra A, Stanchina ML, Ayas NT. Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis. Arch Intern Med 2003; 163: 565 571. 25 Nguyen AT, Baltzan MA, Small D, Wolkove N, Guillon S, Palayew M. Clinical reproducibility of the Epworth Sleepiness Scale. J Clin Sleep Med 2006; 2: 170 174. 26 Saaresranta T, Polo O. Sleep-disordered breathing and hormones. Eur Respir J 2003; 22: 161 172. 27 Jennum P, Sjøl A. Self-assessed cognitive function in snorers and sleep apneics. An epidemiological study of 1,504 females and males aged 30 60 years: the Dan- MONICA II Study. Eur Neurol 1994; 34: 204 208. 28 Launois SH, Pépin JL, Lévy P, Sleep apnea in the elderly: a specific entity? Sleep Med Rev 2007; 11: 87 97. 29 Lavie P, Herer P, Lavie L. Mortality risk factors in sleep apnoea: a matched case control study. J Sleep Res 2007; 16: 128 134. 30 Lavie L, Lavie P. Smoking interacts with sleep apnea to increase cardiovascular risk. Sleep Med 2008; 9: 247 253. 31 Jennum P, Hein HO, Suadicani P, Sorensen H, Gyntelberg F. Snoring, family history, and genetic markers in men. The Copenhagen Male Study. Chest 1995; 107: 1289 1293. 32 Carmelli D, Bliwise DL, Swan GE, Reed T. Genetic factors in self-reported snoring and excessive daytime sleepiness: a twin study. Am J Respir Crit Care Med 2001; 164: 949 952. 33 Ovchinsky A, Rao M, Lotwin I, Goldstein NA. The familial aggregation of pediatric obstructive sleep apnea syndrome. Arch Otolaryngol Head Neck Surg 2002; 128: 815 818. 34 Riha RL, Gislasson T, Diefenbach K. The phenotype, genotype of adult obstructive sleep apnoea/hypopnoea syndrome. Eur Respir J 2009; 33: 646 655. 35 Grunstein RR, Stenlof K, Hedner JA, Peltonen M, Karason K, Sjostrom L. Two year reduction in sleep apnea symptoms and associated diabetes incidence after weight loss in severe obesity. Sleep 2007; 30: 703 710. 36 Newman AB, Foster G, Givelber R, Nieto FJ, Redline S, Young T. Progression and regression of sleep-disordered breathing with changes in weight: the Sleep Heart Health Study. Arch Intern Med 2005; 165: 2408 2413. 37 Spivak H, Hewitt MF, Onn A, Half EE. Weight loss and improvement of obesity-related illness in 500 U.S. patients following laparoscopic adjustable gastric banding procedure. Am J Surg 2005; 189: 27 32. 38 Fogel RB, Malhotra A, Pillar G, Pittman SD, Dunaif A, White DP. Increased prevalence of obstructive sleep apnea syndrome in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 2001; 86: 1175 1180. 39 Vgontzas AN, Legro RS, Bixler EO, Grayev A, Kales A, Chrousos GP. Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance. J Clin Endocrinol Metab 2001; 86: 517 520. 40 McNicholas WT, Bonsigore MR. Sleep apnoea as an independent risk factor for cardiovascular disease: current 912 VOLUME 33 NUMBER 4 EUROPEAN RESPIRATORY JOURNAL

P. JENNUM AND R.L. RIHA EPIDEMIOLOGY OF SLEEP APNOEA evidence, basic mechanisms and research priorities. Eur Respir J 2007; 29: 156 178. 41 Blankfield RP, Hudgel DW, Tapolyai AA, Zyzanski SJ. Bilateral leg edema, obesity, pulmonary hypertension, and obstructive sleep apnea. Arch Intern Med 2000; 160: 2357 2362. 42 Sajkov D, Wang T, Saunders NA, Bune AJ, Mcevoy RD. Continuous positive airway pressure treatment improves pulmonary hemodynamics in patients with obstructive sleep apnea. Am J Respir Crit Care Med 2002; 165: 152 158. 43 McArdle N, Riha RL, Vennelle M, et al. Sleep-disordered breathing as a risk factor for cerebrovascular disease: a case control study in patients with transient ischemic attacks. Stroke 2003; 34: 2916 2921. 44 Neau JP, Paquereau J, Meurice JC, Chavagnat JJ, Gil R. Stroke and sleep apnoea: cause or consequence? Sleep Med Rev 2002; 6: 457 469. 45 Valham F, Mooe T, Rabben T, Stenlund H, Wiklund U, Franklin KA. Increased risk of stroke in patients with coronary artery disease and sleep apnea: a 10-year followup. Circulation 2008; 118: 955 960. 46 Hsu CY, Vennelle M, Li HY, Engleman HM, Dennis MS, Douglas NJ. Sleep-disordered breathing after stroke: a randomised controlled trial of continuous positive airway pressure. J Neurol Neurosurg Psychiatry 2006; 77: 1143 1149. 47 de Miguel J, Cabello J, Sánchez-Alarcos JM, Alvarez-Sala R, Espinós D, Alvarez-Sala JL. Long-term effects of treatment with nasal continuous positive airway pressure on lung function in patients with overlap syndrome. Sleep Breath 2002; 6: 3 10. 48 Mansfield D, Naughton MT. Effects of continuous positive airway pressure on lung function in patients with chronic obstructive pulmonary disease and sleep disordered breathing. Respirology 1999; 4: 365 370. 49 Chan CS, Woolcock AJ, Sullivan CE. Nocturnal asthma: role of snoring and obstructive sleep apnea. Am Rev Respir Dis 1988; 137: 1502 1504. 50 Engleman HM, Kingshott RN, Martin SE, Douglas NJ. Cognitive function in the sleep apnea/hypopnea syndrome (SAHS). Sleep 2000; 23: Suppl. 4, S102 S108. 51 Engleman HM, Hirst WS, Douglas NJ. Under reporting of sleepiness and driving impairment in patients with sleep apnoea/hypopnoea syndrome. J Sleep Res 1997; 6: 272 275. 52 Terán-Santos J, Jiménez-Gómez A, Cordero-Guevara J. The association between sleep apnea and the risk of traffic accidents. Cooperative Group Burgos-Santander. N Engl J Med 1999; 340: 847 851. 53 Barbé, Pericás J, Muñoz A, Findley L, Antó JM, Agustí AG. Automobile accidents in patients with sleep apnea syndrome. An epidemiological and mechanistic study. Am J Respir Crit Care Med 1998; 158: 18 22. 54 George CF, Smiley A. Sleep apnea and automobile crashes. Sleep 1999; 22: 790 795. 55 Ulfberg J, Carter N, Edling C. Sleep-disordered breathing and occupational accidents. Scand J Work Environ Health 2000; 26: 237 242. 56 Lindberg E, Carter N, Gislason T, Janson C. Role of snoring and daytime sleepiness in occupational accidents. Am J Respir Crit Care Med 2001; 164: 2031 2035. 57 Koskenvuo M, Partinen M, Kaprio J. Snoring and disease. Ann Clin Res 1985; 17: 247 251. 58 Jennum P, Hein HO, Suadicani P, Gyntelberg F. Cardiovascular risk factors in snorers. A cross-sectional study of 3,323 men aged 54 to 74 years: the Copenhagen Male Study. Chest 1992; 102: 1371 1376. 59 Jennum P, Sjøl A. Snoring, sleep apnoea and cardiovascular risk factors: the MONICA II Study. Int J Epidemiol 1993; 22: 439 444. 60 Davies DP, Rodgers H, Walshaw D, James OF, Gibson GJ. Snoring, daytime sleepiness and stroke: a case-control study of first-ever stroke. J Sleep Res 2003; 12: 313 318. 61 Mohsenin V. Sleep-related breathing disorders and risk of stroke. Stroke 2001; 32: 1271 1278. 62 Bassetti CL, Milanova M, Gugger M. Sleep-disordered breathing and acute ischemic stroke: diagnosis, risk factors, treatment, evolution, and long-term clinical outcome. Stroke 2006; 37: 967 972. 63 Ellen RL, Marshall SC, Palayew M, Molnar FJ, Wilson KG, Man-Son-Hing M. Systematic review of motor vehicle crash risk in persons with sleep apnea. J Clin Sleep Med 2006; 2: 193 200. 64 Tan MC, Ayas NT, Mulgrew A, et al. Cost-effectiveness of continuous positive airway pressure therapy in patients with obstructive sleep apnea hypopnea in British Columbia. Can Respir J 2008; 15: 159 165. 65 Pack AI, Pien GW. How much do crashes related to obstructive sleep apnea cost? Sleep 2004; 27: 369 370. 66 Gurubhagavatula I, Nkwuo JE, Maislin G, Pack AI. Estimated cost of crashes in commercial drivers supports screening and treatment of obstructive sleep apnea. Accid Anal Prev 2008; 40: 104 115. 67 Tarasiuk A, Greenberg-Dotan S, Simon T, Tal A, Oksenberg A, Reuveni H. Low socioeconomic status is a risk factor for cardiovascular disease among adult obstructive sleep apnea syndrome patients requiring treatment. Chest 2006; 130: 766 773. 68 Li X, Sundquist K, Sundquist J. Socioeconomic status and occupation as risk factors for obstructive sleep apnea in Sweden: a population-based study. Sleep Med 2008; 9: 129 136. 69 McDaid C, Griffin S, Weatherley H. The continuous positive airway pressure for the treatment of obstructive sleep apnoea hypopnoea syndrome: a systematic review and economic analysis. Health Technol Assess 2009; 13: 1 142. 70 Douglas NJ, George CF. Treating sleep apnoea is cost effective. Thorax 2002; 57: 93. 71 Peker Y, Hedner J, Johansson A, Bende M. Reduced hospitalization with cardiovascular and pulmonary disease in obstructive sleep apnea patients on nasal CPAP treatment. Sleep 1997; 20: 645 653. 72 Mar J, Rueda JR, Durán-Cantolla J, Schechter C, Chilcott J. The cost-effectiveness of ncpap treatment in patients with moderate-to-severe obstructive sleep apnoea. Eur Respir J 2003; 21: 515 522. 73 Albarrak M, Banno K, Sabbagh AA, et al. Utilization of healthcare resources in obstructive sleep apnea syndrome: a 5-year follow-up study in men using CPAP. Sleep 2005; 28: 1306 1311. 74 Bing MH, Moller LA, Jennum P, Mortensen S, Skovgaard LT, Lose G. Prevalence and bother of nocturia, and causes of sleep interruption in a Danish population of men and women aged 60 80 years. BJU Int 2006; 98: 599 604. c EUROPEAN RESPIRATORY JOURNAL VOLUME 33 NUMBER 4 913

EPIDEMIOLOGY OF SLEEP APNOEA P. JENNUM AND R.L. RIHA 75 Epstein LJ, Dorlac GR. Cost-effectiveness analysis of nocturnal oximetry as a method of screening for sleep apnea hypopnea syndrome. Chest 1998; 113: 97 103. 76 Collop NA, Anderson WM, Boehlecke B, et al. Clinical guidelines for the use of unattended portable monitors in the diagnosis of obstructive sleep apnea in adult patients. Portable Monitoring Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med 2007; 3: 737 747. 77 Jennum P, Santamaria J. Report of an EFNS task force on management of sleep disorders in neurologic disease (degenerative neurologic disorders and stroke). Eur J Neurol 2007; 14: 1189 1200. 914 VOLUME 33 NUMBER 4 EUROPEAN RESPIRATORY JOURNAL